Liver X receptors (LXRs), members of the nuclear receptor super-family, regulate expression of genes relating to cholesterol metabolism and homeostasis. Two LXR isoforms, i.e., LXRα and LXRβ, have been identified. While LXRα expression is restricted to liver, kidney, intestine, fat tissue, macrophages, lung, and spleen, LXRβ is expressed in almost all tissues and organs.
LXRs modulate lipid metabolism and ApoE gene expression. Accumulation of lipids in arteries causes atherosclerosis and accumulation of lipids in the cornea results in corneal arcus. See, e.g., Zech et al., Lipids in Health and Disease 2008, 7:7. Deficiency of ApoE gene expression attributes to diseases such as Alzheimer's disease. See, e.g., Artiga et al., Human Molecular Genetics 1998, 7: 1887. Thus, LXR agonists can be used to treat atherosclerosis, corneal arcus, and Alzheimer's disease.
LXRs also stimulate insulin secretion and inhibit inflammation and autoimmune reactions. See Jamroz-Wiśniewska et al., Postepy Hig Med. Dosw. 2007, 61:760. Thus, LXR agonists can be used to treat diabetes (e.g., Type 1 diabetes) and inflammatory/autoimmune disorders.
Further, it has been found that activation of LXRs leads to inhibition of the hedgehog signaling pathway, which plays a key role in developing cancer in various organs (e.g., brain, lung, blood, prostate, breast, and skin) See, e.g., Watkin et al., Nature, 2003, 442: 313-317. Thus, LXR agonists can also be used to treat cancer. See, e.g., Chu et al., Journal of biomedical science, 2007, 14(5): 543-553.